555 research outputs found

    Withdrawal from Repeated Cocaine Alters Dopamine Transporter Protein Turnover in the Rat Striatum

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    ABSTRACT Several studies have shown that repeated cocaine administration, followed by withdrawal, alters dopamine transporter (DAT) levels in the rat. These changes must arise from changes in either transporter protein production or degradation, or both. Previously, our laboratory developed an approach to measure the synthesis rate, degradation rate constant, and half-life of DAT in the rat striatum and nucleus accumbens after administration of the irreversible dopamine transporter ligand, RTI-76 . These initial studies showed that: 1) the half-life of the transporter was between 2 and 3 days in these two brain regions; 2) pretreatment with dopamine D1 and D2 receptor agonists and antagonists over several days differentially altered DAT half-lives in the striatum and nucleus accumbens; and 3) pretreatment with cocaine for several days increased the half-life of DAT by decreasing the degradation rate constant in both brain regions. In the present study, we determined that repeated pretreatment (10 days) with 20 mg/kg cocaine (i.p.) and a subsequent withdrawal period (10 days) alters the dopamine transporter turnover in the rat striatum, but not in the nucleus accumbens. Cocaine pretreatment and withdrawal reduced the half-life of the transporter protein from 2.1 days to 0.94 day in the striatum, but did not alter the half-life of 2.2 days in the nucleus accumbens. The results indicate the complex and long-lasting effects of cocaine administration on cellular processes. The mechanism(s) of these effects remains to be elucidated

    Secure Real-Time Monitoring and Management of Smart Distribution Grid Using Shared Cellular Network

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    The electricity production and distribution is facing two major changes. First, the production is shifting from classical energy sources such as coal and nuclear power towards renewable resources such as solar and wind. Secondly, the consumption in the low voltage grid is expected to grow significantly due to expected introduction of electrical vehicles. The first step towards more efficient operational capabilities is to introduce an observability of the distribution system and allow for leveraging the flexibility of end connection points with manageable consumption, generation and storage capabilities. Thanks to the advanced measurement devices, management framework, and secure communication infrastructure developed in the FP7 SUNSEED project, the Distribution System Operator (DSO) now has full observability of the energy flows at the medium/low voltage grid. Furthermore, the prosumers are able to participate pro-actively and coordinate with the DSO and other stakeholders in the grid. The monitoring and management functionalities have strong requirements to the communication latency, reliability and security. This paper presents novel solutions and analyses of these aspects for the SUNSEED scenario, where the smart grid ICT solutions are provided through shared cellular LTE networks

    Kappa Opioid receptor-induced aversion requires p38 MAPK activation in VTA dopamine neurons

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    The endogenous dynorphin-κ opioid receptor (KOR) system encodes the dysphoric component of the stress response and controls the risk of depression-like and addiction behaviors; however, the molecular and neural circuit mechanisms are not understood. In this study, we report that KOR activation of p38α MAPK in ventral tegmental (VTA) dopaminergic neurons was required for conditioned place aversion (CPA) in mice. Conditional genetic deletion of floxed KOR or floxed p38α MAPK by Cre recombinase expression in dopaminergic neurons blocked place aversion to the KOR agonist U50,488. Selective viral rescue by wild-type KOR expression in dopaminergic neurons of KOR(−/−) mice restored U50,488-CPA, whereas expression of a mutated form of KOR that could not initiate p38α MAPK activation did not. Surprisingly, while p38α MAPK inactivation blocked U50,488-CPA, p38α MAPK was not required for KOR inhibition of evoked dopamine release measured by fast scan cyclic voltammetry in the nucleus accumbens. In contrast, KOR activation acutely inhibited VTA dopaminergic neuron firing, and repeated exposure attenuated the opioid response. This adaptation to repeated exposure was blocked by conditional deletion of p38α MAPK, which also blocked KOR-induced tyrosine phosphorylation of the inwardly rectifying potassium channel (GIRK) subunit Kir3.1 in VTA dopaminergic neurons. Consistent with the reduced response, GIRK phosphorylation at this amino terminal tyrosine residue (Y12) enhances channel deactivation. Thus, contrary to prevailing expectations, these results suggest that κ opioid-induced aversion requires regulation of VTA dopaminergic neuron somatic excitability through a p38α MAPK effect on GIRK deactivation kinetics rather than by presynaptically inhibiting dopamine release. SIGNIFICANCE STATEMENT Kappa opioid receptor (KOR) agonists have the potential to be effective, nonaddictive analgesics, but their therapeutic utility is greatly limited by adverse effects on mood. Understanding how KOR activation produces dysphoria is key to the development of better analgesics and to defining how the endogenous dynorphin opioids produce their depression-like effects. Results in this study show that the aversive effects of κ receptor activation required arrestin-dependent p38α MAPK activation in dopamine neurons but did not require inhibition of dopamine release in the nucleus accumbens. Thus, contrary to the prevailing view, inhibition of mesolimbic dopamine release does not mediate the aversive effects of KOR activation and functionally selective κ opioids that do not activate arrestin signaling may be effective analgesics lacking dysphoric effects

    The litmus test of pride: analysing the emergence of the Belgrade “Ghost” pride in the context of EU accession

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    The transformation of lesbian, gay, bisexual, and transgender (LGBT) rights into a “standard for civilisation” has not been without consequences. With LGBT Pride parades becoming a symbol for Europeanness in the European Union (EU) accession process, this article asks how the litmus test character of Belgrade Pride has transformed LGBT politics in Serbia. Empirically, the analysis provides an in-depth analysis of how Serbia’s EU accession process has shaped the politics of Belgrade Pride between 2001 and 2015 and vice versa. It is argued that the international symbolic usage of Pride is no innocent practice as it has foreclosed its local politicality. Indeed, whilst Belgrade Pride became politicised as a litmus test in the EU accession process, domestically it developed into an apolitical ritualised event devoid of LGBT politics

    Early Identification and Prevention of the Spread of Ebola - United States

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    In response to the 2014-2016 Ebola virus disease (Ebola) epidemic in West Africa, CDC prepared for the potential introduction of Ebola into the United States. The immediate goals were to rapidly identify and isolate any cases of Ebola, prevent transmission, and promote timely treatment of affected patients. CDC\u27s technical expertise and the collaboration of multiple partners in state, local, and municipal public health departments; health care facilities; emergency medical services; and U.S. government agencies were essential to the domestic preparedness and response to the Ebola epidemic and relied on longstanding partnerships. CDC established a comprehensive response that included two new strategies: 1) active monitoring of travelers arriving from countries affected by Ebola and other persons at risk for Ebola and 2) a tiered system of hospital facility preparedness that enabled prioritization of training. CDC rapidly deployed a diagnostic assay for Ebola virus (EBOV) to public health laboratories. Guidance was developed to assist in evaluation of patients possibly infected with EBOV, for appropriate infection control, to support emergency responders, and for handling of infectious waste. CDC rapid response teams were formed to provide assistance within 24 hours to a health care facility managing a patient with Ebola. As a result of the collaborations to rapidly identify, isolate, and manage Ebola patients and the extensive preparations to prevent spread of EBOV, the United States is now better prepared to address the next global infectious disease threat.The activities summarized in this report would not have been possible without collaboration with many U.S. and international partners (http://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/partners.html)

    The Spectrometer/Telescope for Imaging X-rays (STIX)

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    Aims. The Spectrometer Telescope for Imaging X-rays (STIX) on Solar Orbiter is a hard X-ray imaging spectrometer, which covers the energy range from 4 to 150 keV. STIX observes hard X-ray bremsstrahlung emissions from solar flares and therefore provides diagnostics of the hottest (⪆10 MK) flare plasma while quantifying the location, spectrum, and energy content of flare-accelerated nonthermal electrons. Methods. To accomplish this, STIX applies an indirect bigrid Fourier imaging technique using a set of tungsten grids (at pitches from 0.038 to 1 mm) in front of 32 coarsely pixelated CdTe detectors to provide information on angular scales from 7 to 180 arcsec with 1 keV energy resolution (at 6 keV). The imaging concept of STIX has intrinsically low telemetry and it is therefore well-suited to the limited resources available to the Solar Orbiter payload. To further reduce the downlinked data volume, STIX data are binned on board into 32 selectable energy bins and dynamically-adjusted time bins with a typical duration of 1 s during flares. Results. Through hard X-ray diagnostics, STIX provides critical information for understanding the acceleration of electrons at the Sun and their transport into interplanetary space and for determining the magnetic connection of Solar Orbiter back to the Sun. In this way, STIX serves to link Solar Orbiter’s remote and in-situ measurements
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